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Structural insights into the recognition of substrates and activators by the OSR1 kinase.

Villa F, Goebel J, Rafiqi FH, Deak M, Thastrup J, Alessi DR, van Aalten DM
EMBO Rep 8 839-45 (2007)
Cited: 64 times
EuropePMC logo PMID: 17721439

Abstract

The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline/alanine-rich kinase (SPAK) are key enzymes in a signalling cascade regulating the activity of Na(+)/K(+)/2Cl(-) co-transporters (NKCCs) in response to osmotic stress. Both kinases have a conserved carboxy-terminal (CCT) domain, which recognizes a unique peptide (Arg-Phe-Xaa-Val) motif present in OSR1- and SPAK-activating kinases (with-no-lysine kinase 1 (WNK1) and WNK4) as well as its substrates (NKCC1 and NKCC2). Here, we describe the structural basis of this recognition event as shown by the crystal structure of the CCT domain of OSR1 in complex with a peptide containing this motif, derived from WNK4. The CCT domain forms a novel protein fold that interacts with the Arg-Phe-Xaa-Val motif through a surface-exposed groove. An intricate web of interactions is observed between the CCT domain and an Arg-Phe-Xaa-Val motif-containing peptide derived from WNK4. Mutational analysis shows that these interactions are required for the CCT domain to bind to WNK1 and NKCC1. The CCT domain structure also shows how phosphorylation of a Ser/Thr residue preceding the Arg-Phe-Xaa-Val motif results in a steric clash, promoting its dissociation from the CCT domain. These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates.

Reviews - 2v3s mentioned but not cited (3)

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Articles - 2v3s mentioned but not cited (8)

  1. A novel Ste20-related proline/alanine-rich kinase (SPAK)-independent pathway involving calcium-binding protein 39 (Cab39) and serine threonine kinase with no lysine member 4 (WNK4) in the activation of Na-K-Cl cotransporters. Ponce-Coria J, Markadieu N, Austin TM, Flammang L, Rios K, Welling PA, Delpire E. J. Biol. Chem. 289 17680-17688 (2014)
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Reviews citing this publication (22)

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Articles citing this publication (31)

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  2. Short-term stimulation of the thiazide-sensitive Na+-Cl- cotransporter by vasopressin involves phosphorylation and membrane translocation. Mutig K, Saritas T, Uchida S, Kahl T, Borowski T, Paliege A, Böhlick A, Bleich M, Shan Q, Bachmann S. Am. J. Physiol. Renal Physiol. 298 F502-9 (2010)
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  4. Crystal structure of domain-swapped STE20 OSR1 kinase domain. Lee SJ, Cobb MH, Goldsmith EJ. Protein Sci. 18 304-313 (2009)
  5. WNK1 is required for mitosis and abscission. Tu SW, Bugde A, Luby-Phelps K, Cobb MH. Proc. Natl. Acad. Sci. U.S.A. 108 1385-1390 (2011)
  6. On the substrate recognition and negative regulation of SPAK, a kinase modulating Na+-K+-2Cl- cotransport activity. Gagnon KB, Delpire E. Am. J. Physiol., Cell Physiol. 299 C614-20 (2010)
  7. Caenorhabditis elegans WNK-STE20 pathway regulates tube formation by modulating ClC channel activity. Hisamoto N, Moriguchi T, Urushiyama S, Mitani S, Shibuya H, Matsumoto K. EMBO Rep. 9 70-75 (2008)
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  10. OSR1-sensitive renal tubular phosphate reabsorption. Pathare G, Föller M, Daryadel A, Mutig K, Bogatikov E, Fajol A, Almilaji A, Michael D, Stange G, Voelkl J, Wagner CA, Bachmann S, Lang F. Kidney Blood Press. Res. 36 149-161 (2012)
  11. The mechanism of beta-adrenergic preconditioning: roles for adenosine and ROS during triggering and mediation. Salie R, Moolman JA, Lochner A. Basic Res. Cardiol. 107 281 (2012)
  12. Behavioral analysis of Ste20 kinase SPAK knockout mice. Geng Y, Byun N, Delpire E. Behav. Brain Res. 208 377-382 (2010)
  13. Interactions with WNK (with no lysine) family members regulate oxidative stress response 1 and ion co-transporter activity. Sengupta S, Tu SW, Wedin K, Earnest S, Stippec S, Luby-Phelps K, Cobb MH. J. Biol. Chem. 287 37868-37879 (2012)
  14. Molecular determinants of hyperosmotically activated NKCC1-mediated K+/K+ exchange. Gagnon KB, Delpire E. J. Physiol. (Lond.) 588 3385-3396 (2010)
  15. Short forms of Ste20-related proline/alanine-rich kinase (SPAK) in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage. Markadieu N, Rios K, Spiller BW, McDonald WH, Welling PA, Delpire E. J. Biol. Chem. 289 29273-29284 (2014)
  16. Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK. Taylor CA, Juang YC, Earnest S, Sengupta S, Goldsmith EJ, Cobb MH. Biochemistry 54 5063-5071 (2015)
  17. OSR1-sensitive regulation of Na+/H+ exchanger activity in dendritic cells. Pasham V, Rotte A, Yang W, Zelenak C, Bhandaru M, Föller M, Lang F. Am. J. Physiol., Cell Physiol. 303 C416-26 (2012)
  18. Rafoxanide and Closantel Inhibit SPAK and OSR1 Kinases by Binding to a Highly Conserved Allosteric Site on Their C-terminal Domains. AlAmri MA, Kadri H, Alderwick LJ, Simpkins NS, Mehellou Y. ChemMedChem 12 639-645 (2017)
  19. Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2 domain. Moon TM, Correa F, Kinch LN, Piala AT, Gardner KH, Goldsmith EJ. J. Mol. Biol. 425 1245-1252 (2013)
  20. The Ste20 kinases SPAK and OSR1 travel between cells through exosomes. Koumangoye R, Delpire E. Am. J. Physiol., Cell Physiol. 311 C43-53 (2016)
  21. Implications of the N-terminal heterogeneity for the neuronal K-Cl cotransporter KCC2 function. Markkanen M, Ludwig A, Khirug S, Pryazhnikov E, Soni S, Khiroug L, Delpire E, Rivera C, Airaksinen MS, Uvarov P. Brain Res. 1675 87-101 (2017)
  22. OSR1-sensitive small intestinal Na+ transport. Pasham V, Pathare G, Fajol A, Rexhepaj R, Michael D, Pakladok T, Alesutan I, Rotte A, Föller M, Lang F. Am. J. Physiol. Gastrointest. Liver Physiol. 303 G1212-9 (2012)
  23. Development of WNK signaling inhibitors as a new class of antihypertensive drugs. Ishigami-Yuasa M, Watanabe Y, Mori T, Masuno H, Fujii S, Kikuchi E, Uchida S, Kagechika H. Bioorg. Med. Chem. 25 3845-3852 (2017)
  24. Functional identification of protein phosphatase 1-binding consensus residues in NBCe1-B. Lee KP, Kim HJ, Yang D. Korean J. Physiol. Pharmacol. 22 91-99 (2018)
  25. C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity. Murillo-de-Ozores AR, Rodríguez-Gama A, Bazúa-Valenti S, Leyva-Ríos K, Vázquez N, Pacheco-Álvarez D, De La Rosa-Velázquez IA, Wengi A, Stone KL, Zhang J, Loffing J, Lifton RP, Yang CL, Ellison DH, Gamba G, Castañeda-Bueno M. J. Biol. Chem. 293 12209-12221 (2018)
  26. Genome-Wide Identification and Expression Analysis of WNK Kinase Gene Family in Acorus. Ji H, Wu Y, Zhao X, Miao JL, Deng S, Li S, Gao R, Liu ZJ, Zhai J. Int J Mol Sci 24 17594 (2023)
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